ABSTRACT
The optimal regimen for treatment of Mycobacterium avium complex (MAC) disease has not been established. Eighty-five AIDS patients with disseminated MAC disease were randomized to receive a three-drug regimen of clarithromycin, rifabutin or clofazimine, and ethambutol. Two dosages of clarithromycin, 500 or 1,000 mg twice daily (b.i.d.), were compared. The Data and Safety Monitoring Board recommended discontinuation of the clarithromycin dosage comparison and continuation of the rifabutin vs. clofazimine comparison. After a mean follow-up of 4.5 months, 10 (22%) of 45 patients receiving clarithromycin at 500 mg b.i.d. had died (70 deaths per 100 person-years) compared with 17 (43%) of 40 patients receiving clarithromycin at 1,000 mg b.i.d. (158 deaths per 100 person-years) (relative risk, 2.43; 95% confidence interval, 1.11-5.34; P = .02). After 10.4 months, 20 (49%) of 41 patients receiving rifabutin had died (81 deaths per 100 person-years) compared with 23 (52%) of 44 patients receiving clofazimine (94 deaths per 100 person-years) (relative risk, 1.20; 95% confidence interval, 0.65-2.19; P = .56). Bacteriologic outcomes were similar among treatment groups. In treating MAC disease in AIDS patients, the maximum dose of clarithromycin should be 500 mg b.i.d.
Subject(s)
AIDS-Related Opportunistic Infections/drug therapy , Anti-Bacterial Agents/adverse effects , Clarithromycin/adverse effects , Drug Therapy, Combination/therapeutic use , Mycobacterium avium-intracellulare Infection/drug therapy , AIDS-Related Opportunistic Infections/microbiology , AIDS-Related Opportunistic Infections/mortality , Adult , Anti-Bacterial Agents/therapeutic use , Antibiotics, Antitubercular/adverse effects , Antibiotics, Antitubercular/therapeutic use , Clarithromycin/therapeutic use , Clofazimine/adverse effects , Clofazimine/therapeutic use , Dose-Response Relationship, Drug , Drug Therapy, Combination/adverse effects , Female , Follow-Up Studies , Humans , Male , Mycobacterium avium Complex , Mycobacterium avium-intracellulare Infection/microbiology , Mycobacterium avium-intracellulare Infection/mortality , Patient Compliance , Prospective Studies , Rifabutin/adverse effects , Rifabutin/therapeutic use , Survivors , Treatment OutcomeSubject(s)
Acupuncture Therapy , Leg/blood supply , Radionuclide Angiography/methods , Sodium Pertechnetate Tc 99m/administration & dosage , Adolescent , Adult , Aged , Female , Humans , Injections, Subcutaneous/methods , Male , Middle Aged , Predictive Value of Tests , Thrombophlebitis/diagnostic imaging , Varicose Veins/diagnostic imaging , Veins/diagnostic imagingABSTRACT
To identify adults with acute nonlymphocytic leukemia at risk for the development of central nervous system involvement, we performed periodic cerebrospinal fluid examinations on patients in remission. Among 58 consecutive patients monitored during first remission, central nervous system leukemia developed in nine (16 percent). Four patients, including one who was symptomatic, had central nervous system leukemia detected simultaneously with marrow relapse. Five additional patients were asymptomatic and continue to have bone marrow remission. Following central nervous system and systemic treatment, two of these five patients have never had relapse, and three had relapse in the bone marrow five, 10, and 21 months later. Factors at diagnosis associated with the subsequent development of central nervous system leukemia were elevated leukocyte count, serum lysozyme and lactate dehydrogenase, extramedullary infiltration including splenomegaly, and monocytic (FAB M4 or M5a) morphology. In six of 17 patients (35 percent) with monocytic morphology, central nervous system leukemia developed compared with only three of 41 patients (7 percent) with other subtypes (p = 0.02). Discriminant analysis identified leukocyte count, splenomegaly, and M4 or M5a morphology as the most important risk factors and led to a mathematical formula that correctly identified 90 percent of the patients. Although the risk of central nervous system leukemia in adults with acute nonlymphocytic leukemia is too low to justify routine prophylaxis, those patients recognized to be at a greater risk should receive prophylaxis or be monitored closely with periodic lumbar punctures.
